The topical administration of pharmaceuticals for ophthalmic indications is generally preferred for ease of use and patient compliance. Aqueous solutions having physiologically-compatible pH and osmolality are representative of delivery systems in this class. However, many pharmaceutical agents are relatively insoluble in aqueous vehicle and must be delivered as a suspension. Often, such agents do not penetrate corneal tissue well. Suspensions can be diluted or flushed from the eye by the tear film before the agent is able to enter the corneal tissue in sufficient concentration.
Accordingly, various techniques have been used to improve the overall bioavailability of sparingly soluble pharmaceutical agents and increase the concentration of such agents in targeted tissues. Increasing the viscosity of topically applied solutions to increase the retention time of the solution on the cornea does not always lead to an increase in bioavailability, and may actually retard penetration of the pharmaceutical agent into the cornea. See, e.g., U.S. patent application Ser. No. 11/429,736, filed May 8, 2006 and entitled “Suspension Formulations of Nepafenac and other Ophthalmic Drugs for the Topical Treatment of Ophthalmic Disorders”.
Ophthalmic compositions have been previously described that utilize galactomannan-borate gelling systems. U.S. Pat. No. 6,403,609 to Asgharian, entitled “Ophthalmic compositions containing galactomannan polymers and borate,” describes such systems and is herein incorporated by reference in its entirety.
Ophthalmic compositions that enhance the corneal penetration of sparingly soluble pharmaceutical agents such as nepafenac have been disclosed in U.S. patent application Ser. No. 11/430,239 filed May 8, 2006 entitled “Suspension Formulations of Nepafenac and other Ophthalmic Drugs for Topical Treatment of Ophthalmic Disorders”. The '239 application describes the use of poloxamer or meroxapol surfactant and a glycol tonicity-adjusting agent in compositions having good corneal permeability of the active pharmaceutical. These compositions do not comprise a carboxyvinyl polymer.
U.S. Pat. No. 5,188,826 discloses an ophthalmic gel suspension for treating dry eye. The suspension compositions remain as a gel in the eye for a prolonged time, and release water and one or more ophthalmic demulcents or vasoconstrictors. The suspension compositions contain a water-insoluble, lightly cross-linked, carboxyl-containing polymer having a particle size of not more than 50 μm in equivalent spherical diameter. The demulcent is preferably at least one of sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, dextran 70, gelatin, glycerin, polyethylene glycol, polysorbate 80, propylene glycol, polyvinyl alcohol or polyvinylpyrrolidone. Particularly preferred as the carboxyl-containing polymer is CARBOPOL® 976. The suspension compositions do not contain a prescription drug.
U.S. Pat. No. 5,192,535 discloses suspension compositions of ophthalmic drugs that have suitably low viscosities to permit easy administration in drop form, but which rapidly gel in the eye to provide sustained drug release. The suspension compositions are formulated at a pH of from about 3 to about 6.5 and contain a water-insoluble, carboxyl-containing polymer prepared by polymerizing one or more carboxyl-containing monoethylenically unsaturated monomers and less than about 5% by weight of a cross-linking agent. CARBOPOL® 976 and polycarbophil are identified as examples of suitable carboxyl-containing polymers. These formulations gel in the eye due to the thermogelling properties of the polymers. Ion exchange resins may be included as one type of adjuvant in the suspension compositions. Demulcents are identified as one of many types of medicaments suitable for use in the suspension compositions.